Hydrocephalus is a common neurological disorder leading to expansion of the cerebral ventricles. Most neonatal cases are of unknown etiology and are likely to display complex inheritance involving multiple genes and environmental factors. We employed a hydrocephalic mouse model of the human ciliopathy Bardet-Biedl Syndrome (BBS) and identified a role for neural progenitors in the pathogenesis of neonatal hydrocephalus.
Abnormal development of NG2+PDGFRα+ neural progenitor cells causes neonatal hydrocephalus in a ciliopathy mouse modelNovember 18th, 2012
March 6th, 2012
The Research Eye Bank at the IVR enables scientists to study common and rare diseases. Scientists at the IVR recently had the first opportunity to characterize eyes from a donor with retinal degeneration due to mutations in the ABCA4 gene. This work, which combined human genetics with histology and state of the art microarray analysis, found that death of photoreceptor cells (rods and cones) occurs in advance of death of the retinal pigment epithelium (RPE).
Vitamins commonly prescribed for age-related macular degeneration reduce inflammation in blood vessel cellsJanuary 12th, 2012
The Age-Related Eye Disease Study (AREDS) combination of vitamins and zinc is commonly recommended to patients with age-related macular degeneration (AMD), but the mechanism whereby this regimen affects the progression of AMD has not been well studied. Wynn Institute scientists examined the effects of an AREDS vitamin solution on cells involved in AMD and found that treatment with vitamin solution reduces the adhesion between white blood cells and the endothelial cells that line blood vessels (see photo below), suggesting that inflammation in eyes with AMD may be reduced by the treatment.
December 24th, 2011
An essential step in the development of therapy for an inherited disease is to carefully characterize a cohort of affected patients to define the anatomical and temporal features of the disease. Such a study can identify the tissues that are the most relevant target for therapy as well as the points in the disease course where various treatments would have the greatest opportunity for benefit with the lowest risk.
November 3rd, 2011
The mechanisms controlling BBSome trafficking and the cargo proteins transported by the BBSome are not well understood. We hypothesized that by utilizing tandem affinity purification (TAP) we could identify novel regulators and cargos of the BBSome. Therefore, we generated transgenic mice expressing BBSome subunits with a TAP tag and performed tandem affinity purification using tissue from these mice to identify a novel protein, leucine-zipper transcription factor-like 1 (LZTFL1), as a BBSome interacting protein.
Reduction of ER stress via a chemical chaperone prevents disease phenotypes in a mouse model of primary open angle glaucomaAugust 8th, 2011
Mutations in myocilin (MYOC) are the most common genetic cause of primary open angle glaucoma (POAG), but the mechanisms underlying MYOC-associated glaucoma are not fully understood. Efforts to develop an animal model of POAG were not successful until we developed a transgenic mouse model (Tg-MYOCY437H) by inserting a human mutation into the mouse gene and expressed the mutant mouse gene in relevant eye tissues.
July 18th, 2011
Development of treatments for Mendelian diseases will often require identification of disease-causing mutations and elucidation of the effect of these mutations on protein function. Wynn Institute scientists combined two relatively new technologies, exome sequencing and patient-derived induced pluripotent stem cells (iPSCs), to identify a new retinitis pigmentosa gene and demonstrate the pathogenic effect of its most common mutation.
June 23rd, 2011
Two researchers in the Institute for Vision Research at the University of Iowa Carver College of Medicine have been awarded grants by Research to Prevent Blindness, an organization that supports research into the causes, treatment and prevention of diseases that threaten vision.
Transplantation of Adult Mouse iPS Cell-Derived Photoreceptor Precursors Restores Retinal Structure and Function in Degenerative MiceApril 29th, 2011
This study was designed to determine whether adult mouse induced pluripotent stem cells (iPSCs), could be used to produce retinal photoreceptor precursor cells that could be used for retinal transplantation to restore retinal function in retinal degenerative hosts. iPSCs were generated using adult dsRed mouse dermal fibroblasts via retroviral induction of the transcription factors Oct4, Sox2, KLF4 and c-Myc.
January 26th, 2010
In previous work, we identified a stable complex (BBSome) consisting of eight proteins that binds PCM-1 and tubulin. Our data indicate that the BBSome performs an essential ciliogenic function at the basal body and inside the cilium. The cilia-related function of the BBSome is mediated, at least in part, through the Rab8 GDP/GTP exchange factor (Rabin8). The relationship between the BBSome and other BBS proteins was unknown.